CCK AND MIDBRAIN DA SYSTEMS--SPECIFICITY OF ACTIONS

CCK 和中脑 DA 系统——行动的特异性

• 批准号: 3381213
• 负责人: ARTHUR S FREEMAN
• 金额: $ 2.06万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381213
• 关键词: 6 hydroxydopamine; amygdala; chloral hydrate; cholecystokinin; dopamine; electrophysiology; experimental brain lesion; ketamine; mesencephalon; neurons; neuropharmacology; neurophysiology; phencyclidine; serotonin

Cholecystokinin octapeptide (CCK-8) is present within midbrain dopamine (DA)-containing neurons and appears to act as a cotransmitter. The importance of these DA neurons in current hypotheses of the etiology and treatment of several neurological and psychiatric disorders requires that their physiology and their pharmacological responsiveness be well understood. In recent years, much has been learned about the receptor subtypes which mediate the effects of CCK-8 on DA neurons, but much remains to be learned about the scope and sites of CCK-8 actions In the midbrain. The studies proposed in this application are intended to evaluate possible sites of action for modulatory effects of CCK-8 on the electrophysiological activity of DA neurons in anesthetized rats. The serotonergic input to the midbrain from the dorsal raphe nucleus Influences the electrophysiological activity of DA neurons. In the first set of proposed experiments, Interactions of CCK-8 with the effects of dorsal raphe nucleus stimulation (and with serotonin itself on nigrostriatal and mesoaccumbal DA neuronal activity will be evaluated. Non-DA interneurons in the substantia nigra pars reticulata (SNr). Influence the activity of nigral DA neurons and may be accessible to locally released CCK-8. The SNr is also the source of non-DA nigrothalamic and nigrotectal neurons which are important links in the extrapyramidal motor system. Thus, the effects of CCK-8 on the activity of SNr interneurons and antidromically identified nigrothalamic and nigrotectal neurons will be determined. The neurotoxin 6-OHDA causes the degeneration of DA neurons and is used to produce an animal model of Parkinson's disease. The pharmacological responsiveness of the remaining DA neurons has been shown to be greatly altered. Because of the intimate relationship between CCK-8 and DA, it is possible that the responsiveness of remaining DA neurons to CCK-8 is changed in the 6-OHDA-lesioned rat. Such a change In responsiveness would have important implications for the regulation of DA neuronal function in the lesioned rat and, by inference, certain disease states. In the last set of experiments, the effects of CCK-8 on remaining DA neurons in the 6-OHDA-lesioned rat will be tested. The effects of the lesions on DA levels and CCK-8 levels in the midbrain DA cell body region and in DA cell projection sites will also be determined.

中脑多巴胺内存在胆囊动蛋白八肽（CCK-8） （DA） - 含神经元，似乎充当共晶剂。 这 这些DA神经元在病因的当前假设中的重要性 治疗几种神经和精神疾病需要 他们的生理学和药理反应良好 理解。 近年来，有关受体的知识已有很多 介导CCK-8对DA神经元的影响的亚型，但仍然存在很多 要了解中脑CCK-8动作的范围和地点。 本应用中提出的研究旨在评估可能 CCK-8对电生理的调节作用位点 麻醉大鼠DA神经元的活性。 从背raphe核向中脑输入的5-羟色胺能输入 影响DA神经元的电生理活性。 在第一个 一组提出的实验，CCK-8与 背侧raphe核刺激（以及5-羟色胺本身 将评估NigroStriatal和中间DA神经元活性。 黑质nigra pars reticulata（SNR）中的非da中间神经元。 影响nigral da神经元的活性，并且可以访问 本地发布的CCK-8。 SNR也是非Da nigrothalamic的来源 和骨直肠神经元，它们是腹膜跨膜的重要链接 电机系统。 因此，CCK-8对SNR活性的影响 中间神经元和反蒙格洛氏菌和黑骨直肠 神经元将被确定。 神经毒素6-OHDA导致变性 da神经元的生产帕金森氏症动物模型 疾病。 其余DA神经元的药理反应性 已被证明发生了很大的改变。 由于亲密关系 在CCK-8和DA之间，剩余的响应能力可能 在6- OHDA仪器的大鼠中，DA神经元更改为CCK-8。 这样的变化 响应能力将对监管具有重要意义 病变的大鼠中的DA神经元功能，并通过推断某些疾病 国家。 在最后一组实验中，CCK-8对剩余的影响 将测试6- OHDA的大鼠中的DA神经元。 效果 中脑DA细胞体区域DA水平和CCK-8水平的病变 在DA细胞投影位点也将确定。